ADA 2 Deficiency: A Diagnosis 28 Years in the Making

Introduction: Adenosine deaminase 2 deficiency (DADA2), reported for the first time in 2014, is a monogenic autoinflammatory disease characterized by early-onset vasculopathy, systemic inflammation, multiorgan involvement and immunodeficiency. There were many misdiagnosis before the discovery of this entity, which negatively influenced its management.

Case report: We describe a case of a 3-month-old that presented to the Emergency Department with irritability, vomiting, facial paralysis and hypertension. Family history of consanguinity, autoimmunity (mother with systemic juvenile idiopathic arthritis and Behçet’s disease) and chronic kidney disease. A full etiologic investigation for renovascular hypertension with proteinuria was performed without conclusions. By the age of 7, she started having episodes of prolonged fever associated with abdominal pain, hepatosplenomegaly, polyarthritis, episcleritis, proteinuria, Raynaud’s phenomenon and livedo racemosa. At 9 years old, she had a hemorrhagic stroke which was considered to be due to a brain cavernoma, from which she fully recovered. At this point, we had performed an extensive investigation excluding most infectious, immune, metabolic, genetic and oncologic etiologies. Her presumed diagnosis was of a form of systemic polyarteritis nodosa. The disease ultimately progressed to renal insufficiency secondary to AA amyloidosis. Upon her mother’s death of hemorrhagic stroke, the possibility of DADA2 was raised. The diagnosis was made at 28 years old after a functional analysis revealed absence of plasma ADA2 activity, which was confirmed by genetic testing.

Discussion and conclusions: A delayed diagnosis of DADA2 provides a unique insight to the natural history of the disease and the wide range of phenotypic variability within the DADA2 spectrum. Although it might prove challenging given the variety of clinical manifestations, a patient with livedo and thrombotic events, especially with suggestive family history, should raise awareness for the disease. Early recognition is essential for the management and prevention of major complications.